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ERPs Cognitive Dysfunction and Treatment Response of Geriatric Depression

ERPs 认知功能障碍和老年抑郁症的治疗反应

基本信息

批准号：
8089485
负责人：
GEORGE S ALEXOPOULOS
金额：
$ 30.74万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-07-01 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8089485
关键词：
Adverse effects Affect Aftercare Age Aging Anisotropy Anterior Antidepressive Agents Brain Caring Clinical Clinical Trials Clinical dementia rating scale Color Complement 3a Complement 3b Complement 3d Complement 4b Complement component C4a Depressed mood Diffusion Magnetic Resonance Imaging Discrimination Disease remission Dorsal Dose EP300 gene Elderly Electroencephalography Emotional Escitalopram Evaluation Event Evolution Functional disorder Goals Impaired cognition Impairment Lateral Lead Left Literature Major Depressive Disorder Mediating Memory Mental Depression Methodology Neuropsychological Tests Outcome Patients Peat Performance Pharmaceutical Preparations Placebos Process Psychopathology Quality of life Recurrence Relapse Research Personnel Residual state Risk Sampling Series Severities Specificity Structure Testing Time Translational Research age related base cingulate cortex complement C2a complement C2b depressive symptoms disability executive function follow-up functional disability functional status geriatric depression health care service utilization heuristics indexing instrumental activity of daily living neuroimaging novel response therapy development treatment planning treatment response treatment trial white matter

项目摘要

DESCRIPTION (provided by applicant): This study focuses on frontal processing abnormalities in geriatric depression and their relationship to treatment response. Its aims evolved empirically from our studies suggesting that executive dysfunction (a clinical expression of frontal dysfunction) is: 1. Common in geriatric depression; 2. associated with a clinical presentation of depression consistent with frontal dysfunction and with microstructural white matter (WM) abnormalities lateral to the anterior cingulate cortex (ACC); and 3. contributes to disability. We also observed that indices of frontal dysfunction, including ACC dysfunction, predict poor response of late-life depression to antidepressants. A logical next step was a search for frontal processing abnormalities associated with poor antidepressant response. To this end, we conducted ERP studies following tasks activating the dorsal and the rostral ACC subdivisions, which led to the proposed hypotheses. The primary hypotheses postulate that large error-related negativity (ERN) and small error positivity (Pe) amplitude following the Color-Word Stroop response-inhibition task and an "emotional Go/Nogo" discrimination task of sad and neutral words predict change in depressive symptoms, remission and response rates and change in function in depressed elders treated with escitalopram. We will explore whether ERN and Pe amplitudes change during the treatment course and examine whether their change is associated with change in executive functions and in severity of depression. These hypotheses will be tested in 120 subjects with major depression stratified according to age (65-74 and 75-84 years) and executive dysfunction (Stroop), who will undergo a 12-week, controlled, open escitalopram trial with a target daily dose of 20 mg after a 2 week drug washout, placebo lead-in. The subjects will have EEG recording at baseline and weeks 4 and 8, and a comprehensive systematic evaluation of psychopathology and of clinical parameters that influence the course of depression (baseline, 8 weeks, and 12 weeks). Depressive symptomatology, functional status, and side effects will be rated weekly. On heuristic level, we expect that our findings will provide the impetus for translational research leading to novel treatment development and a change in clinical trials methodology. On a clinical level, identifying ERP abnormalities associated with poor antidepressant response and persistent disability may inform treatment planning, especially if the implicated ERP parameters are correlated with scores of simple-to-administer neuropsychological tests. Such patients could be targeted for a vigilant clinical follow-up and a comprehensive treatment plan including a plan for successive pharmacological trials.

描述（由申请人提供）：本研究的重点是老年抑郁症的额叶处理异常及其与治疗反应的关系。它的目标从我们的研究经验发展而来，表明执行功能障碍（额叶功能障碍的临床表现）是：1。常见于老年抑郁症; 2.与符合额叶功能障碍和前扣带皮层（ACC）外侧微结构白色物质（WM）异常的抑郁症的临床表现相关;和3.造成残疾。我们还观察到，额叶功能障碍的指数，包括ACC功能障碍，预测抗抑郁药对晚年抑郁症的反应不佳。合乎逻辑的下一步是寻找与抗抑郁反应不良相关的额叶处理异常。为此，我们进行了ERP的研究任务激活背侧和喙侧ACC的细分，这导致了提出的假设。主要假设假设，大错误相关负波（ERN）和小错误正波（Pe）振幅以下的颜色词Stroop反应抑制任务和“情绪去/Nogo”的悲伤和中性词的歧视任务预测抑郁症状的变化，缓解率和响应率和功能的变化在抑郁症老年人治疗艾司西酞普兰。我们将探讨ERN和Pe振幅是否在治疗过程中发生变化，并检查其变化是否与执行功能和抑郁症严重程度的变化有关。这些假设将在120例根据年龄（65-74岁和75-84岁）和执行功能障碍（Stroop）分层的重度抑郁症受试者中进行检验，这些受试者将接受为期12周的对照开放性艾司西酞普兰试验，目标日剂量为20 mg，药物洗脱2周后，安慰剂导入。受试者将在基线和第4周和第8周进行EEG记录，并对影响抑郁症病程的精神病理学和临床参数（基线、第8周和第12周）进行全面系统评价。每周对抑郁症、功能状态和副作用进行评级。在启发式水平上，我们希望我们的研究结果将为转化研究提供动力，从而导致新的治疗方法的开发和临床试验方法的改变。在临床层面上，识别与抗抑郁反应差和持续残疾相关的ERP异常可能会为治疗计划提供信息，特别是如果所涉及的ERP参数与简单的神经心理学测试评分相关。这类患者可以作为警惕性临床随访和全面治疗计划的目标，包括连续药理学试验计划。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Ventromedial syndrome with normal cognitive functioning in vascular depression.

血管性抑郁症中具有正常认知功能的腹内侧综合征。

DOI：
10.1176/appi.ajp.2014.14050595
发表时间：
2014
期刊：
The American journal of psychiatry
影响因子：
0
作者：
Manning,KevinJ;Gunning,FaithM;McGovern,AmandaR;Kotbi,Nabil;Alexopoulos,GeorgeS
通讯作者：
Alexopoulos,GeorgeS

A model for intervention research in late-life depression.